Validating the impact of a molecular subtype in ovarian cancer on outcomes: A study of theOVCADConsortium

Abstract

Most patients with epithelial ovarian cancer (EOC) are diagnosed at advanced stage and have a poor prognosis. However, a small proportion of these patients will survive, whereas others will die very quickly. Clinicopathological factors do not allow precise identification of these subgroups. Thus, we have validated a molecular subclassification as new prognostic factor in EOC. One hundred and ninety-four patients with Stage II-IV EOC were characterized by whole-genome expression profiling of tumor tissues and were classified using a published 112 gene set, derived from an International Federation of Gynecology and Obstetrics (FIGO) stage-directed supervised classification approach. The 194 tumor samples were classified into two subclasses comprising 95 (Subclass 1) and 99 (Subclass 2) tumors. All nine FIGO II tumors were grouped in Subclass 1 (P = 0.001). Subclass 2 (54% % of advancedstage tumors) was significantly correlated with peritoneal carcinomatosis and non-optimal debulking. Patients with Subclass 2 tumors had a worse overall survival for both serous and non-serous histological subtypes, as revealed by univariate analysis (hazard ratios [HR] of 3.17 and 17.11, respectively; P 0.001) and in models corrected for relevant clinicopathologic parameters (HR 2.87 and 12.42, respectively; P 0.023). Significance analysis of microarrays revealed 2082 genes that were differentially expressed in advanced-grade serous tumors of both subclasses and the focal adhesion pathway as the most deregulated pathway. In the present validation study, we have shown that, in advanced-stage serous ovarian cancer, two approximately equally large molecular subtypes exist, independent of classical clinocopathological parameters and presenting with highly different whole-genome expression profiles and a markedly different overall survival. Similar results were obtained in a small cohort of patients with non-serous tumors. (Cancer Sci 2012; 103: 1334-1341

Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread

“…Despite its heterogeneity, most patients are treated with standard therapy regardless of molecular differences. However, recent studies suggest treatment response differences according to molecular characteristics such as mutation status [19] or gene expression signatures [18, 20, 21]. Thus, understanding the molecular basis of HGSOC and peritoneal tumor spread would be of immense importance.…”

Interval Debulking Surgery in Patients with Federation of Gynecology and Obstetrics (FIGO) Stage IIIC and IV Ovarian Cancer

“…Patients with platinum-resistant disease would be identified and spared an extensive surgical procedure on the basis of their poor outcome. Although biobanking has firmly been implemented by most clinicians today, NAC offers the additional opportunity, as seen in other tumor entities, to directly investigate the molecular effects of chemotherapy on the tumor [9]. Already, different groups with experience in NAC have started building extensive biobanks with paired tissues before and after chemotherapy, trying to understand vessel growth, immune response or tumor regression during treatment [10,11,12,13].…”

Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high‐grade serous ovarian cancer

“…[2][3][4][5][6][7] Several studies on gene profiling of the primary tumor using microarray technology have described potential genes/pathways contributing to chemotherapy resistance and their association with risk stratification/overall survival. [8][9][10][11][12][13][14][15][16][17][18] Unlike the clinical impact of gene profiling on treatment decisions for several solid tumors there has been limited progress with the prediction or the clinical management of recurrent HGSOC.…”